Shenzhen Geno-Immune Medical Institute is conducting a Phase I/II clinical trial of gene therapy for treating X-linked adrenoleukodystrophy using a high-safety, high-efficiency, self-inactivating lentiviral vector TYF-ABCD1 to functionally correct the defective gene. The objectives are to evaluate the safety and efficacy of the gene transfer clinical protocol.
X-linked adrenoleukodystrophy (X-ALD) is a devastating neurological disorder caused by mutations in the ABCD1 gene that encodes a peroxisomal ATP-binding cassette transporter (ABCD1). ABCD1 is responsible for transport of CoA-activated very long-chain fatty acids (VLCFA) into the peroxisome for degradation. X-ALD is clinically characterized by two main phenotypes: adrenomyeloneuropathy (AMN) and the inflammatory cerebral ALD.
This diease presents most commonly in males. Approximately 50% of heterozygote females show some symptoms later in life. Approximately two-thirds of ALD patients will present with the childhood cerebral form of the disease, which is the most severe form. The disease is characterized by normal development in early childhood, followed by rapid degeneration to a vegetative state. ALD patients are normally treated with haematopoietic stem cell transplantation (HSCT) from a matched healthy donor.
However, HSCT must be performed at a very early stage of the disease, which limits the therapeutic opportunies for juvenile or adult forms of ALD. This trial aims to treat ALD using a safety and efficiency improved self-inactivating lentiviral vector carrying a functional ABCD1 gene to correct the genetic defect. By Intracerebral injection to delivery the lentiviral vector with a normal ALD gene to correct the pathologies associated with this genetic defect.
The primary objectives are to evaluate the safety of the advanced self-inactivating lentiviral vector TYF-ABCD1, the in-vivo gene transfer clinical protocol and the efficacy of degradative metabolite in patients at the time of treatment, assessment of vector integration sites, and finally the long-term correction of patients' disease beheviors.